title: Antifibrotic role of chemokine CXCL9 in experimental chronic pancreatitis induced by trinitrobenzene sulfonic acid in rats.
abstract: Chemokines have been shown to play an important role in the pathogenesis of pancreatitis, but the role of chemokine CXCL9 in pancreatitis is poorly understood. The aim of this study was to investigate whether CXCL9 was a modulating factor in chronic pancreatitis. Chronic pancreatitis was induced in Sprague-Dawley rats by intraductal infusion of trinitrobenzene sulfonic acid (TNBS) and CXCL9 expression was assessed by immunohistochemistry, Western blot analysis and enzyme linked immunosorbent assay (ELISA). Recombinant human CXCL9 protein (rCXCL9), neutralizing antibody and normal saline (NS) were administered to rats with chronic pancreatitis by subcutaneous injection. The severity of fibrosis was determined by measuring hydroxyproline in pancreatic tissues and histological grading. The effect of rCXCL9 on activated pancreatic stellate cells (PSCs) in vitro was examined and collagen 1α1, TGF-β1 and CXCR3 expression was assessed by Western blot analysis in isolated rat PSCs. Chronic pancreatic injury in rats was induced after TNBS treatment and CXCL9 protein was markedly upregulated during TNBS-induced chronic pancreatitis. Although parenchymal injury in the pancreas was not obviously affected after rCXCL9 and neutralizing antibody administration, rCXCL9 could attenuate fibrogenesis in TNBS-induced chronic pancreatitis in vivo and exerted antifibrotic effects in vitro, suppressing collagen production in activated PSCs. In conclusion, CXCL9 is involved in the modulation of pancreatic fibrogenesis in TNBS-induced chronic pancreatitis in rats, and may be a therapeutic target in pancreatic fibrosis.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Jiangsu, China.
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Shen
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Congying
authors.initials: C
authors.lastname: Chen
authors.forename: Huili
authors.initials: H
authors.lastname: Lu
authors.forename: Guoyong
authors.initials: G
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Shunying
authors.initials: S
authors.lastname: Zhu
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Wu
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Qian
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Rong
authors.initials: R
authors.lastname: Wan
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D049109:Cell Proliferation; D054370:Chemokine CXCL9 / Q000096:biosynthesis / Q000378:metabolism*; D024042:Collagen Type I / Q000096:biosynthesis; D005355:Fibrosis; D006909:Hydroxyproline / Q000032:analysis; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D058954:Pancreatic Stellate Cells / Q000378:metabolism; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054367:Receptors, CXCR3 / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D057134:Antibodies, Neutralizing; C505723:CXCL9 protein, rat; D054370:Chemokine CXCL9; D024042:Collagen Type I; C515189:Cxcr3 protein, rat; D054367:Receptors, CXCR3; D053773:Transforming Growth Factor beta1; D014302:Trinitrobenzenesulfonic Acid; D006909:Hydroxyproline
keywords: CXCL9; Chronic pancreatitis; Fibrosis; Pancreatic stellate cells (PSCs); Rats